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Genetic variations in human G protein-coupled receptors: Implications for drug therapy

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The AAPS Journal : Volume 3, Issue 2, June 2001

The AAPS Journal : Volume 3, Issue 1, March 2001

The AAPS Journal : Volume 2

The AAPS Journal : Volume 1

Genetic variations in human G protein-coupled receptors: Implications for drug therapy

Content Provider	Springer Nature Link
Author	Sadee, Wolfgang Hoeg, Elen Lucas, Julie Wang, Danxin
Copyright Year	2001
Abstract	Numerous genes encode G protein-coupled receptors (GPCRs)-a main molecular target for drug therapy. Estimates indicate that the human genome contains approximately 600 GPCR genes. This article addresses therapeutic implications of sequence variations in GPCR genes. A number of inactivating and activating receptor mutations have been shown to cause a variety of (mostly rare) genetic disorders. However, pharmacogenetic and pharmacogenomic studies on GPCRs are scarce, and therapeutic relevance of variant receptor alleles often remains unclear. Confounding factors in assessing the therapeutic relevance of variant GPCR alleles include 1) interaction of a single drug with multiple closely related receptors, 2) poorly defined binding pockets that can accommodate drug ligands in different orientations or at alternative receptor domains, 3) possibility of multiple receptor conformations with distinct functions, and 4) multiple signaling pathways engaged by a single receptor. For example, antischizophrenic drugs bind to numerous receptors, several of which might be relevant to therapeutic outcome. Without knowing accurately what role a given receptor subtype plays in clinical outcome and how a sequence variation affects drug-induced signal transduction, we cannot predict the therapeutic relevance of a receptor variant. Genome-wide association studies with single nucleotide polymorphisms could identify critical target receptors for disease susceptibility and drug efficacy or toxicity.
Starting Page	54
Ending Page	80
Page Count	27
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	3
Issue Number	3
e-ISSN	15221059
Language	English
Publisher	Springer New York
Publisher Date	2001-09-01
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	G Protein-Coupled Receptors Drug Therapy Pharmacogenomics Pharmacogenetics Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

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